DESCRIPTION (adapted from the applicant's description): The precise mechanisms by which reentry is maintained during ventricular fibrillation (VF) and how it is altered by ischemia, infarction and heart failure are unknown. This information is vital to prevent sudden cardiac death. This application proposes to evaluate several different mechanisms proposed for VF maintenance by performing transmural mapping in animals. Besides mapping and quantifying activation sequences during VF, intramural monophasic action potential (MAP) electrodes will be used to quantify repolarization. Specific Aim 1: Use 3-D activation mapping to quantify intramural reentry during VF. VF will be mapped simultaneously from up to 870 intramural and 484 epicardial electrodes in open-chest pigs to quantify 3-D reentry in normal hearts and hearts with ischemia and infarction. The hypotheses will be tested that (1) conduction block occurs more frequency when wavefronts travel parallel rather than perpendicular to the long axis of myofibers, (2) a certain minimal length of block is necessary to initiate reentry, (3) focal activation occurs during VF, caused by reentry involving the Purkinje-muscle junction, (4) reentry circuits are formed by bifurcation, "sproing," or rapid drift of rotor filaments, (5) reentry can be initiated by vortex shedding at the sharp boundaries of an infarct scar and (6) an acute ischemic region does not contribute to VF maintenance. Specific Aim 2: Validate MAP recordings from plunge needles. MAP recordings will be compared with microelectrode and optical recordings. It will be determined if the MAP electrodes can measure activation and action potential duration without altering them in guinea pigs and rabbits. Specific Aim 3: Use 3-D MAP mapping to compare the relative roles of the non-uniform dispersion of recovery and the restitution properties of the ventricles in causing block and reentry during VF. The relative importance of three hypotheses for the mechanism of VF maintenance will be evaluated in dogs: (1) the non-uniform dispersion of recovery causes block when a wavefront in an area of lesser refractoriness encounters an adjacent region of greater refractoriness; (2) restitution properties where activation occurs on a steep portion of the restitution curve causes oscillation in coupling intervals which becomes so great that block occurs; and (3) reentry occurs where a wavefront propagates perpendicular to the wavetail of refractoriness of the previous wavefront. The hypotheses will be tested that heart failure caused by patchy fibrosis decreases VF organization while heart failure cause by rapid pacing increases it.